Project #1[unreadable] [unreadable] IL-10 has been identified as a critical regulator of Th2 immunity but mechanisms for controlling Th2 effector function remain unclear. IL-10 also has paradoxical effects on Th2-associated allergic and fibrotic responses, with IL-10 deficiency resulting in increased Th2-driven inflammation but reduced airway hyperreactivity (AHR), mucus hypersecretion and fibrosis. We demonstrated that the interleukin-13 receptor alpha 2 (IL-13Ra2) was responsible for the reduced AHR, mucus production, and fibrosis in BALB/c IL-10-/- mice. Using a novel model of allergic asthma, we demonstrated that IL-10 and IL-13Ra2 coordinately suppress Th2-mediated inflammation and pathology, respectively. Although IL-10 was identified as the dominant anti-inflammatory mediator, studies with double IL-10/IL-13Ra2-deficient mice illustrated an indispensable role for IL-13Ra2 in the suppression of AHR, mucus production, and fibrosis. Thus, IL-10 and IL-13Ra2 are both required to control chronic Th2-driven pathological responses.[unreadable] [unreadable] Project #2[unreadable] [unreadable] To determine whether sIL-4Ra and/or sIL-13Ra2 levels change in concentration and/or saturation during the course of a Th2 response, these parameters were followed in C57BL/6 mice following infection of wild-type, IL-13-deficient, and IL-4/IL-13-double-deficient mice. These results showed that IL-4 and IL-13 secretion in infected mice both contributed to the increase in serum sIL-13Ra2 levels, with little increase seen in mice that are deficient in both IL-4 and IL-13. These studies also showed that the soluble IL-13Ra2 is rapidly saturated following infection with S. mansoni, reaching peak saturation levels (90-100%) approximatley 9 wk post-infection. These observations suggest sIL-13Ra2 limits direct effects of IL-13 to the site of IL-13 production and forms a stable complex with IL-13 that can modify the quality, as well as the intensity of an allergic or helminth-induced type-2 inflammatory response.